In the field of blood transfusion, so-called leukocyte-free blood transfusion in which a blood product is transfused after removing leukocytes contained in the blood product has been widely used. This is because it was found that relatively slight side effects accompanying blood transfusion, such as headache, nausea, chill, or nonhemolytic fever reaction, or serious side effects which seriously affect a recipient, such as alloantigen sensitization, viral infection, or post-transfusion graft-versus-host disease (GVHD), are mainly caused by leukocytes contained in the blood product used for blood transfusion.
A method of removing leukocytes from the blood product is roughly classified into two kinds of methods of a centrifugation method in which leukocytes are separated and removed using a centrifuge by utilizing specific gravity difference among the blood components, and a filter method in which leukocytes are removed by using a filter material comprising a porous element such as fiber material or porous material having continuous pores. Of these, the filter method is widely used at present due to the advantages such as excellent leukocyte removal capability, easy operation, and a low cost.
A filter method, specifically, processing of leukocyte-containing liquid such as a blood product using a leukocyte-removing filter, has been performed in many cases beside the bed at the blood transfusion. In recent years, because of improving quality control of leukocyte-free products and efficiency of leukocyte removal operations, it is more common to process the blood in blood centers before storing the blood products.
Conventionally, a hard container of polycarbonate or the like filled with filter elements made from nonwoven fabric or porous material has widely been used as a leukocyte-removing filter. However, 1) since the container used in such a filter does not have steam permeability, it has been difficult to use a high-pressure vapor sterilization method, which is a widely accepted sterilization method in blood collection-separation sets. In addition, 2) when leukocytes are removed from two or more blood component products obtained by centrifugation of a whole blood using a so-called closed system in which a leukocyte-removing filter is incorporated in a blood separation set, the leukocyte-removing filter is also centrifuged together with the blood separation set. In such a case, a hard container has a risk of damaging bags and tubes, or the hard container itself may not withstand the stress during centrifugation and may collapse. As a method for solving these problems, flexible leukocyte-removing filters using a container made of a flexible material have been developed (see JP-A-6-335516, JP-A-7-67952, JP-A-7-267871 and JP-T-8-507000, for example,).
Usually, when blood is filtered through these leukocyte-removing filters, a bag containing a blood product to be filtered is placed on a location about 100 cm higher than the filter in order to filter the blood product by the action of gravity. As another demand for the leukocyte-removing filter in the market, reducing working time by processing a desired amount of blood in a short period of time has been desired in recent years.
For this reason, in addition to the method of filtering a blood product by the action of gravity which has been conventionally widely accepted, a method of filtrating blood in a shorter period of time by increasing the filtration speed of blood by feeding the blood to the leukocyte-removing filter under pressure by pumping the blood to be filtered has been studied.
In such a filtration method of feeding blood to a leukocyte-removing filter comprising a flexible container by pressurizing the blood with a pump and the like, a pressure drop arises due to resistance of the material of the leukocyte-removing filter during filtration, causing the space on the filter inlet side to be positively pressurized to expand the containers like a balloon. A force acting to rip the leukocyte-removing-filter material from the containers at the junction thereof is constantly created and such a force has a possibility of exploding the leukocyte-removing filter.
As one of the means to prevent such ripping, a method of increasing pressure resistance by housing the filter comprising a flexible container in a reinforced box or a cover made from a plastic or the like of which the volume is smaller than the volume of the filter when the filter is expanded has been proposed (WO 90/15660 pamphlet).
However, when a leukocyte-removing filter comprising a flexible container is stored in such a reinforcement box and blood is fed to the leukocyte-removing filter comprising a flexible container by a pump or the like under pressure, the leukocyte-removing-filter material is pressed against the container on the outlet port side due to a pressure drop generated by resistance of the leukocyte-removing-filter material. In such a state, a leukocyte-removing-filter material closely attaches to the outlet port side container and precludes the blood flow.
JP-A-2001-149444 discloses an invention in which the filter comprising a flexible container is stored in a hard holder. In order to prevent adhesion of the flexible container with the hard holder, projections such as ribs with a width of 1 mm to 3 mm and a height of 1 mm to 3 mm are provided on the inner surface of the holder at intervals of 2 mm to 6 mm. However, when blood is filtered at a high flow rate by being pressurized by a pump or the like using this hard holder, the outlet port side container against which the leukocyte-removing-filter material is pressed expands and comes into the clearance formed by two or more ribs provided inside the holder, but does not form a sufficient space for blood to flow between the leukocyte-removing-filter material and the outlet port side container, making it difficult to prevent the flow of blood from being inhibited.
As a method for solving the problem of filter adhesion, a method of preventing adhesion by inserting a soft polyvinyl chloride tube called a “connecting rod” between the filter material and outlet port side container (European Patent No. 0526678), a method of preventing adhesion of the leukocyte-removing-filter material with the outlet port side container by providing concavo-convex irregularities with a depth of 0.2 mm to 2 mm on the internal surface of the soft container (JP-A-11-216179), a method of inserting a screen made of nit fiber (WO 95/17236 pamphlet), and the like have been proposed. However, even when the leukocyte-removing filter comprising flexible containers is placed inside the reinforced box or holder described in WO 90/15660 pamphlet or JP-A-2001-149444 and blood is filtered at a high flow rate by being pressurized by a pump or the like, the leukocyte-removing-filter material adheres to the outlet port side container and a sufficient space through which the blood flows cannot be produced between the leukocyte-removing-filter material and the outlet port side container. It was thus found that it is difficult to prevent a flow of blood from being obstructed.
Moreover, in a filtration method in which blood is pressurized by a pump or the like and fed into a leukocyte-removing filter comprising a flexible container, a method of restricting the volume of the leukocyte-removing filter comprising a flexible container by providing a volume restriction board having a groove connecting outside of the flexible container toward the blood outlet port has been proposed as disclosed in JP-A-2003-052808. Although excellent flow characteristics of blood can be ensured according to the method described in JP-A-2003-052808, further improvement in respect of prevention of nonuniformity of blood flow within the filter, improvement of filtration efficiency, and the like has been desired.
As mentioned above, when conducting a high speed filtration method in which blood is filtered by being fed to a leukocyte-removing filter comprising flexible containers at a high flow rate by being pressurized using a pump or the like in order to filter a large amount of blood in a short period of time in conventional technology, there have been possibilities of filter breakage and a decrease in leukocyte removal capability due to inhibition and nonuniformity of a blood flow. It was difficult to simultaneously attain 1) efficiently increasing leukocyte removal capability and 2) effectively utilizing the filtration area by preventing nonuniformity of blood flow.